Novel sebum secretion inhibitory agent

ABSTRACT

The present invention relates to a novel sebum secretion inhibitor and use thereof for the production of cosmetic and pharmaceutical, notably dermatological, compositions, intended for preventing and/or reducing the secretion of sebum and notably of squalene.

The present invention relates to a novel sebum secretion inhibitor anduse thereof for the production of cosmetic and pharmaceutical, notablydermatological, compositions intended to prevent and/or reduce thesecretion of sebum and notably of squalene.

Sebum is produced by the sebaceous glands of the skin and is constitutedof a mixture of lipids intended notably to protect the skin againstdrying out, against microbes by acidification, and to preserve itsflexibility. Squalene or (E)2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, generallyknown by the names Spinacene and Suprene, is one of the lipids that ispresent in large amounts and is characteristic of human sebum.

Although the secretion of sebum is useful because of these skinprotecting functions, it gives the skin, especially when it isexcessive, an appearance which is often described as shiny, dull, orgreasy, and sometimes causes dilatation of the pores and/or theformation of blackheads, manifestations that are often perceived asunaesthetic and/or unpleasant and/or uncomfortable. Moreover, thisseborrhoea can be the cause of real pathologies such as seborrhoeiceczema, and/or hypersecretion in nursing infants (commonly known as“milk crust”).

Numerous actives are available in the fields of cosmetics anddermatology for preventing and/or reducing the secretion of sebumdirectly. These agents, called seboregulators, directly reduce theproduction of sebum by the sebaceous glands, for example zinc gluconateand azelaic acid. Other agents are also used for their indirect actionon the secretion of sebum, in particular exfoliating agents, stimulatorsof cell renewal, agents with astringent and/or matifying action byabsorption of sebum.

At present, however, the applicant knows of no active that is capable ofproviding, in a satisfactory manner, an effect on the secretion of sebumthat is at the same time visible, rapid and durable, without causing arebound effect, or irritation of the skin and without loss of itsradiance. It is the intention of the present invention to identify anovel inhibitor of the secretion of sebum, in particular of squalene,for use as an alternative to the actives available on the market.Identifying a sebum secretion inhibitor that in addition is able toprevent and/or reduce the secretion of sebum in a visible, rapid andlong-lasting manner, and advantageously without causing a rebound effectand/or without irritating the skin and/or without a loss of its radiancenotably by complexing with the sebum is thus of considerable interestcosmetically and/or pharmaceutically, notably dermatologically.

According to the present invention, it was discovered particularlysurprisingly and unexpectedly that the Orthosiphon stamineus extract cansolve all of these technical problems. It has in fact been discoveredthat the Orthosiphon stamineus extract can prevent and/or reduce thesecretion of sebum and notably of squalene very effectively.

Orthosiphon stamineus is a plant belonging to the genus Orthosiphon, inthe Lamiaceae family. It is commonly called “Java Tea”. Extracts of thisplant have already been described in cosmetic applications for awhitening, antioxidant or antimicrobial effect (JP2000095663). Moreover,in general, plants belonging to the genus Orthosiphon have also beendescribed in the treatment of prostatic hypertrophy (WO2005087245).

None of the known properties of this extract, however, suggested itseffect for preventing and/or limiting the secretion of sebum, and inparticular of squalene as discovered in the present invention.

The Orthosiphon stamineus extract notably has the advantage that it isnot irritant, it does not complex with sebum, and it is effective veryquickly, quite especially on skin of the Caucasian and/or Asian type.Moreover, apart from its action in preventing and/or reducing thesecretion of sebum, Orthosiphon stamineus extract has the advantage ofpreserving and/or of improving the radiance of the complexion. This isdue notably to the fact that it does not complex with the sebum, doesnot scour the skin and in particular does not attack it, like someagents of the prior art.

The extract acts instead on regulating the secretion of sebum by thesebaceous gland directly and with a lasting, long-term effect. This hasthe advantage that the natural radiance of the complexion is preserved.Moreover, the Orthosiphon stamineus extract improves the radiance of thecomplexion by preventing and/or reducing skin imperfections linked to ahigh level of sebum production. It has notably been observed that theextract according to the invention refines the grain of the skin byreducing the pore size and making it more even.

Some of these properties of the Orthosiphon stamineus extract accordingto the invention will notably be demonstrated in more detail in theexamples supplied below concerning the secretion of sebum, and inparticular of squalene.

The present invention thus relates to the cosmetic use of an Orthosiphonstamineus extract for preventing and/or reducing and/or delaying thesecretion of sebum, in particular of squalene and for preventing and/orreducing the unaesthetic and/or unpleasant and/or uncomfortablemanifestations associated with the secretion of sebum, notably forpreventing and/or reducing and/or delaying the dilatation of the poresize of the skin and/or the formation of blackheads and/or the shinyappearance of the skin and/or of the hair and/or comedogenesis.

The present invention also relates to the use of an Orthosiphonstamineus extract for preparing a pharmaceutical, notably dermatologicalcomposition intended to prevent and/or treat at least one pathologyassociated with hyperproduction of sebum, notably of squalene and inparticular pathological hyperseborrhoeas, seborrhoeic eczema and/orhypersecretion in nursing infants and/or any combination thereof.

The present invention also relates to a cosmetic or pharmaceutical,notably dermatological composition comprising an Orthosiphon stamineusextract in combination with at least one agent selected fromseboregulating agents, preferably selected from sarcosine, zincsalicylate, zinc gluconate, azelaic acid and/or their derivatives,and/or at least one agent with a complementary property selected fromexfoliating agents, keratolytic agents, agents stimulating the synthesisof fibronectin, agents for protecting fibroblast growth factor (FGF2),agents stimulating the growth of fibroblasts, an antibacterial agent, asebum absorber, a comedolytic agent, a local antibiotic and any mixturethereof. In a particular embodiment, the Orthosiphon stamineus extractis contained in this cosmetic or pharmaceutical composition at aconcentration between 0.001 and 10% by weight, and advantageouslybetween 0.01 and 5% by weight of the total composition and preferablybetween 0.1 and 3% by weight of the total composition.

The present invention also relates to the use of such a cosmeticcomposition for preventing and/or reducing and/or delaying the secretionof sebum, in particular of squalene and/or for preventing and/orreducing and/or delaying the dilatation of the pore size of the skinand/or the formation of blackheads and/or the shiny appearance of theskin and/or of the hair and/or comedogenesis.

The present invention further relates to the use of such apharmaceutical composition for preventing and/or treating pathologiesassociated with hyperproduction of sebum, notably of squalene, andespecially pathological hyperseborrhoeas, seborrhoeic eczema and/orhypersecretion in nursing infants.

The present invention finally relates to a method of cosmetic careand/or treatment comprising the daily topical application of anOrthosiphon stamineus extract according to the invention or of acosmetic composition according to the invention for preventing and/orreducing and/or delaying the secretion of sebum, in particular ofsqualene and/or for preventing and/or reducing the unaesthetic and/orunpleasant and/or uncomfortable manifestations associated with thesecretion of sebum, notably for preventing and/or reducing and/ordelaying the dilatation of the pore size of the skin and/or theformation of blackheads and/or the shiny appearance of the skin and/orof the hair and/or comedogenesis.

The present invention relates to the cosmetic use of an Orthosiphonstamineus extract for preventing and/or reducing and/or delaying thesecretion of sebum, in particular of squalene, preferably in the form ofa cosmetic composition.

The present invention also relates to the cosmetic use of an Orthosiphonstamineus extract for preventing and/or reducing and/or delayinghyperseborrhoea.

Advantageously, the present invention can also prevent and/or reduce theunaesthetic and/or unpleasant and/or uncomfortable manifestationsassociated with the secretion of sebum, in particular of squalene,notably:

-   -   by preventing and/or reducing and/or delaying the secretion of        sebum, in particular of squalene,    -   by preventing and/or reducing and/or delaying the dilatation of        the pores of the skin,    -   by preventing and/or reducing and/or delaying the formation of        blackheads,    -   by preventing and/or reducing and/or delaying the shiny        appearance of the skin and/or of the hair,    -   and/or by preventing and/or reducing and/or delaying        comedogenesis.

Advantageously, the present invention also provides for the cosmeticcare and/or treatment of skin described as normal, seborrhoeic, greasy,having a greasy tendency and/or mixed, and of hair described as greasyand/or having a greasy tendency.

The present invention further relates to the cosmetic use of anOrthosiphon stamineus extract for the manufacture of a pharmaceutical,notably dermatological composition intended for preventing and/orreducing the secretion of sebum, in particular of squalene.

Advantageously, the present invention makes it possible to preventand/or reduce at least one pathology associated with hyperproduction ofsebum, and in particular of squalene, notably the pathologicalhyperseborrhoeas, seborrhoeic eczema and/or hypersecretion in nursinginfants.

“Sebum inhibitor” means an agent that is able to prevent and/or reducethe secretion of sebum by the sebaceous glands and notably the secretionof squalene.

“Dilatation of the pores of the skin” means an increase in the diameterof the pores of the skin.

“Seboregulating agent” means an agent, plant extract or characterizedmolecule. capable of regulating, and preferably inhibiting the secretionof sebum and notably of squalene by the sebocytes.

The agent according to the invention is an Orthosiphon stamineusextract. This plant belongs to the genus Orthosiphon and to theLamiaceae family and is commonly called “Java Tea”.

The agent according to the invention can be extracted from the wholeplant or from one or more parts of the plant, notably selected from theroot, stem, bark, flower, seed, germ and/or leaf and mixtures thereof.The agent according to the invention is preferably extracted from theleaves of Orthosiphon stamineus.

The extract can then be obtained by the methods of extraction fromplants known in the field of application, for example by maceration ofat least one part of the plant preferably between 1 and 10% (w/w) in asolvent or a mixture of solvents, preferably a protic polar solvent, andadvantageously in water, an alcohol, a glycol, a polyol, awater/alcohol, water/glycol or water/polyol mixture (such as water mixedwith ethanol, glycerol, butylene glycol or other glycols, such asxylitol etc.) from 100/0 to 0/100 (v/v). The extracts obtained are thenpreferably centrifuged and/or filtered and/or distilled in order torecover the active soluble fraction (raw extract).

The plant extract is preferably dissolved in a solvent, notably a polarsolvent, such as water, an alcohol, a polyol, a glycol, or a mixturethereof.

The active substance can be concentrated by evaporation of the solvent,for example by lyophilization or by spraying.

According to an advantageous embodiment, the agent according to theinvention is an extract obtained by hot aqueous extraction, preferablyof the leaves, preferably by percolation then, optionally after a dryingstage. The extract is then solubilized in an aqueous vehicle, preferablywater. The extract is then used in accordance with the presentinvention, optionally after filtration.

According to a preferred embodiment, the agent according to theinvention is an extract obtained by aqueous percolation carried outbetween 30 and 50° C., preferably between 35 and 40° C.

According to the invention, the Orthosiphon stamineus plant extract ispreferably used alone or in a cosmetic or pharmaceutical composition ata concentration between 1.10⁻⁴ and 10% by weight, and advantageouslybetween 1.10⁻⁴ and 5% by weight and more particularly between 1.10⁻³ and3% by weight of the final composition.

As previously mentioned, the Orthosiphon stamineus extract according tothe present invention is preferably used in the form of cosmetic orpharmaceutical, and preferably dermatological compositions.

The compositions according to the invention can contain any suitablesolvent and/or any suitable vehicle and/or any suitable excipient,optionally in combination with other compounds of interest.

Accordingly, for said compositions, the excipient contains for exampleat least one compound selected from the group consisting ofpreservatives, emollients, emulsifiers, surfactants, moisturizers,thickeners, conditioners, matifying agents, stabilizers, antioxidants,texturizing agents, gloss agents, film-forming agents, solubilizers,pigments, dyes, fragrances and sunscreens. These excipients arepreferably selected from the group comprising amino acids andderivatives thereof, polyglycerols, esters, polymers and derivatives ofcellulose, derivatives of lanolin, phospholipids, lactoferrins,lactoperoxidases, sucrose-based stabilizers, the E vitamins andderivatives thereof, natural and synthetic waxes, vegetable oils,triglycerides, unsaponifiables, phytosterols, plant esters, siliconesand derivatives thereof, protein hydrolysates, jojoba oil andderivatives thereof, fat-soluble/water-soluble esters, betaines, amineoxides, plant extracts, saccharose esters, titanium dioxides, glycines,and parabens, and more preferably from the group consisting of butyleneglycol, steareth-2, steareth-21, glycol-15 stearyl ether, cetearylalcohol, phenoxyethanol, methylparaben, ethylparaben, propylparaben,butylparaben, butylene glycol, natural tocopherols, glycerin,dihydroxycetyl sodium phosphate, isopropyl hydroxycetyl ether, glycolstearate, triisononanoin, octyl cocoate, polyacrylamide, isoparaffin,laureth-7, a carbomer, propylene glycol, glycerol, bisabolol, adimethicone, sodium hydroxide, PEG 30-dipolyhydroxystearate,capric/caprylic triglycerides, cetearyl octanoate, dibutyl adipate,grape seed oil, jojoba oil, magnesium sulphate, EDTA, a cyclomethicone,xanthan gum, citric acid, sodium lauryl sulphate, mineral oils andwaxes, isostearyl isostearate, propylene glycol dipelargonate, propyleneglycol isostearate, PEG 8, beeswax, glycerides of hydrogenated palmkernel, glycerides of hydrogenated palm oil, lanolin oil, sesame oil,cetyl lactate, lanolin alcohol, castor oil, titanium dioxide, lactose,saccharose, low-density polyethylene, an isotonic saline solution.

Advantageously, the aforementioned compositions are formulated in a formselected from the group consisting of an aqueous or oily solution, acream or an aqueous gel or an oily gel, notably in a pot or in a tube,notably a shower gel, a shampoo; a milk; an emulsion, a microemulsion ora nanoemulsion, notably oil-in-water or water-in-oil or multiple orsiliconized; a lotion, notably in a glass or plastic bottle or in ameasuring bottle or in an aerosol; an ampoule; a liquid soap; adermatological bar; an ointment: a mousse; an anhydrous product, whichis preferably liquid, pasty or solid, for example in the form of astick; powders.

The term “topical application”, as used here, signifies applying thecomposition according to the present invention to the surface of theskin and/or the mucosae, notably by direct application or by spraying.

Preferably, the Orthosiphon stamineus extract according to theinvention, preferably in the form of a cosmetic composition according tothe invention, is applied to at least one area of the body where thesecretion of sebum is undesirable and/or excessive, in particular to atleast one area of the body where it is uncomfortable, unaesthetic and/orunpleasant, and/or to at least one area displaying hyperseborrhoea, saidarea or areas preferably being a surface of the body selected from theskin of the face, including the forehead, the cheeks and/or the chin, ofthe neck, of the back, of the thorax, of the hands, and/or of the chest.

The cosmetic compositions according to the invention are in particularintended for the cosmetic care and/or treatment of normal skin, greasyskin, skin said to have a greasy tendency, and/or mixed skin.

Preferably, the Orthosiphon stamineus extract according to theinvention, preferably in the form of a pharmaceutical compositionaccording to the invention, is applied to at least one area of the bodywhere the secretion of sebum is excessive, induces and/or is associatedwith at least one pathology, in particular to at least one area of thebody displaying pathological hyperseborrhoea, said area or areaspreferably being a surface of the body selected from the skin of theface, including the forehead, the cheeks and/or the chin, of the neck,of the back, of the thorax, of the hands, and/or of the chest.

The pharmaceutical compositions according to the invention are inparticular intended for the care and/or treatment of pathologicalhyperseborrhoea, seborrhoeic eczema and/or hypersecretion in nursinginfants.

The term “suitable cosmetic or dermatological vehicle”, as used here,signifies that the composition or its components are suitable for use incontact with human skin without causing toxicity, incompatibility,instability, an allergic response, or their equivalents.

Numerous cosmetically active ingredients are known by a person skilledin the art for improving the health and/or the physical appearance ofthe skin. A person skilled in the art is able to formulate cosmetic ordermatological compositions to obtain the best effects. Furthermore, thecompounds described in the present invention can have a synergisticeffect when they are combined with one another. These combinations arealso covered by the present invention. The CTFA Cosmetic IngredientHandbook, Second Edition (1992) describes various cosmetic andpharmaceutical ingredients currently used in the cosmetic andpharmaceutical industry, which are suitable in particular for topicalapplication. Examples of these classes of ingredients include, withoutbeing limited thereto, the following compounds: abrasives, absorbents,compounds for aesthetic purposes such as fragrances, pigments, dyes,essential oils, astringents, etc. (for example: clove oil, menthol,camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazeldistillate), anti-acne agents; anti-flocculating agents, antifoamingagents, antimicrobial agents (for example: iodopropyl butylcarbamate),antioxidants, binders, biological additives, buffering agents, swellingagents, chelating agents, additives, biocidal agents, denaturants,thickeners, and vitamins, and derivatives or equivalents thereof.film-forming materials, polymers, opacifiers, pH adjusters, reducingagents, depigmenting or lightening agents (for example: hydroquinone,kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbylglucosamine), and conditioning agents (for example: humectants).

Particularly advantageously, the Orthosiphon stamineus extract accordingto the invention can be used, optionally in a cosmetic orpharmaceutical, preferably dermatological, composition, preferably thosepreviously described, as the only active agent, notably as the onlyseboregulating active agent or in combination with one or more otheractive agents selected from:

1) another cosmetic and/or dermatological seboregulating agent,preferably sarcosine, zinc gluconate, zinc salicylate, azelaic acidand/or their derivatives, and/or mixtures thereofand/or2) an agent with complementary properties:

-   -   an exfoliating and/or keratolytic agent, in particular        alpha-hydroxy acids (AHA) notably salicylic acid, optionally in        combination with acacia proteins, malic acid, optionally        together with almond proteins, glycolic acid; lactic acid and/or        their derivatives; and/or mixtures thereof    -   an agent for stimulating the synthesis of fibronectin, in        particular a maize extract, such an extract notably being        marketed by the applicant under the name Deliner™    -   an agent for protecting the fibroblast growth factor (FGF2) of        the extracellular matrix against its degradation and/or its        denaturation, notably an extract of Hibiscus abelmoschus such as        described in the patent application in the name of the applicant        filed under number FR0654316 and/or a fibroblast growth        stimulating agent, for example a fermented soya extract        containing peptides, known under the name Phytokine™ marketed by        the applicant and also described in patent application EP1119344        B1 (Laboratoires Expanscience), and preferably a combination of        these two extracts    -   an agent that stimulates the synthesis of laminin, in particular        a biotechnologically modified malt extract, such an extract        notably being marketed by the applicant under the name        Basaline™:    -   an agent stimulating the expression and/or activity of        hyaluronan synthase 2 (HAS2) such as the plant extracts        described in patent application FR2 893 252 A1 and in particular        an aqueous extract of Galanga (Alpinia galanga);    -   an agent stimulating the synthesis of lysyl oxidase-like (LOXL)        such as those described in patent application FR2855968, and in        particular a dill extract;    -   an agent stimulating the synthesis of intracellular ATP, notably        an extract of alga Laminaria digitata;    -   a sebum absorbing agent, in particular a talc and/or an        absorbent polymer    -   an antibacterial agent notably that described in patent        application FR2863893, and in particular an extract of Boldo,        such an extract notably being marketed by the applicant under        the name Betapur™:    -   an agent with overall anti-ageing action, notably against        pigment spots, in particular nicotinamide or vitamin B3;    -   a comedolytic agent, in particular retinoic acid and one of its        derivatives such as isotretinoin, adapalene and/or 13-cis        retinoic acid and benzoyl peroxide;    -   a local antibiotic agent, in particular erythromycin and/or        clindamycin phosphate; and    -   any mixture thereof.

The agents with complementary properties are preferably selected fromAHA, a maize extract, an extract of Hibiscus abelmoschus, a fermentedsoya extract containing peptides, a biotechnologically modified maltextract, a talc, an absorbent polymer, an extract of Boldo, retinoicacid or a derivative thereof, benzoyl peroxide, erythromycin,clindamycin phosphate and any mixture thereof.

According to the present invention, the combined use of the Orthosiphonstamineus extract according to the invention with the sarcosinemolecule, preferably synthetic and/or its derivatives, preferablywithout another seboregulating agent, is particularly advantageous inthat it provides a complete, effective and long-lasting seboregulatingaction on all skin types, in particular skin described as Caucasianand/or Asian. Sarcosine and/or a derivative thereof is then used at apreferred concentration of between 1.10⁻⁶% and 5% by weight of the totalcomposition, preferably between 1.10⁻⁵% and 0.1% by weight of the totalcomposition and more preferably between 1.10⁻⁴% and 5.10⁻²% by weight ofthe total composition.

The present invention alsO relates to a method of cosmetic care in whichthe Orthosiphon stamineus extract according to the invention is appliedto at least one part of the body, preferably a surface selected from theskin of the face, including the forehead, the cheeks, the chin, theexternal auditory canal, the skin of the neck, of the back, of thethorax, of the hands, and/or of the chest, preferably for preventingand/or reducing the secretion of sebum, in particular of squalene and/orfor preventing and/or reducing the unaesthetic, uncomfortable and/orunpleasant effects from the secretion of sebum.

Advantageously, the Orthosiphon stamineus extract according to theinvention, preferably in the form of a cosmetic composition according tothe invention, is used as a regular and preferably daily topicalapplication for at least 10 days, preferably for 13 days, and morepreferably for at least 20 days.

Other aims, characteristics and advantages of the invention will becomeclear to a person skilled in the art on reading the explanatorydescription, which refers to examples which are given only asillustration and are not intended to limit the scope of the invention inany way.

The examples form an integral part of the present invention and anycharacteristic appearing to be novel relative to any prior art followingfrom the description taken in its entirety, including the examples,forms an integral part of the invention in its function and in itsgenerality.

Thus, each example is of a general scope.

Furthermore, in the examples, all the percentages are given by weight,unless stated otherwise, temperatures are expressed in degrees Celsiusunless stated otherwise, and the pressure is atmospheric pressure,unless stated otherwise.

EXAMPLES Example 1 Preparation of an Orthosiphon stamineus ExtractAccording to the Invention

a) An Orthosiphon stamineus extract is obtained from the leaves bypercolation with water to 5% (w/w), preferably hot percolation, notablyat a temperature between 35 and 40° C.

The percolation time is advantageously between 30 min and 24 hours, withstirring, preferably 10 hours.

The solution is ultrafiltered on ceramic filters with different cutoffthresholds and notably at 0.45 μM.

The extract obtained is then dried notably on a support of themaltodextrin type and then solubilized again in water to 1% (w/w)

b) An Orthosiphon stamineus extract is obtained by extraction from theleaves. This extract is obtained from leaves ground to 7% (wlw) inethanol under reflux or in a mixture with water 75%125%, preferably inwater. Maceration is carried out overnight at 4° C. or room temperatureor preferably for 2 hours at room temperature.

The solution is ultrafiltered on ceramic filters with different cutoffthresholds and notably at 0.45 μM.

The extract obtained is dried and then solubilized again in water to 1%(w/w).

Example 2 Evaluation in vitro of the Effect of an Orthosiphon stamineusExtract According to the Invention on the Secretion of Sebum in NormalHuman Skin

Principle:

The principle of this evaluation is based on the measurement of thebiosynthesis of squalene, a specific tracer of the production of humansebum by the sebocytes, from radiolabelled mevalonic acid.

Experimental protocol:

The products tested were:

-   -   the extract according to the invention was prepared in        accordance with Example 1 a) tested at final concentrations of        from 0.5% to 2% of extract 1 a) in water    -   an aqueous solution of zinc gluconate at 1% (10 mg/mL; 2.2×10⁻²        mol/L) in water is used as positive control    -   no solution as negative control

The following experiment was carried out for each of the productstested:

1) Freshly taken biopsies of human skin (n=3) are incubated in 5 ml ofculture medium in the presence or absence of the test products for 24 h.

2) An amount of radioactive products of 2 μCi of mevalonate 4-¹⁴C isthen added to the biopsies and the whole is incubated again for 24 h.

3) Extraction of the culture media and of the surface of the skin iscarried out with isopropyl ether, then the skin samples are dried andweighed as dry weight.

4) The extraction products are analysed by thin-layer chromatography andthe quantity of metabolites of ¹⁴C-mevalonate (squalene) is evaluated.

Results for the biosynthesis of squalene:

The squalene on the surface of the skin in culture is extracted, thendeposited on HPTLC (high-performance thin layer chromatography) platesand migrated after addition of 10 μg of a squalene standard bydeposition in the presence of heptane as migration solvent. Theradioactivity of the squalene is visualized in a conventional manner.Each radioactive spot corresponding to squalene is scraped onto theHPTLC plates and the radioactivity is measured using a scintillationcounter. Each count was expressed in grams of dry tissue.

The results shown in Table 1 below are those obtained on the extracts ofculture media and are expressed as a percentage relative to theuntreated negative control.

TABLE 1 Results from biosynthesis of squalene for 24 h (dpm ¹⁴C/g drytissue); measurement of the synthesis of squalene on explants of normalhuman skin by transformation of 4-¹⁴[C] mevalonate Measurement ofsqualene synthesis Mean value Standard deviation Negative control 1002.9 Zinc gluconate 1% 76.6 2.5 Extract according to the invention at 2%70.8 2.3

Conclusions

These results show that the Orthosiphon stamineus extract according tothe invention inhibits the formation of squalene and therefore of sebum.

Tests carried out specifically on biopsies of abdominal skin, skin fromthe breast and skin from the face demonstrated that the Orthosiphonstamineus extract according to the invention is equally active on thevarious types of skin.

Example 3 Evaluation in vivo of the Effect of an Orthosiphon stamineusExtract According to the Invention

Principle:

The principle of this evaluation is based on the clinical andinstrumental analysis of samples of secretions of sebum using Sebutape™patches according to the conventional method.

Experimental protocol:

The products tested were:

-   -   the extract according to the invention prepared in accordance        with Example 1 a) is tested at final concentrations of from 0.5%        to 2% of extract 1 a) diluted in water    -   an aqueous solution of zinc gluconate at 1% (10 mg/mL; 2.2×10⁻²        mol/L) in water is used as positive control    -   no solution as negative control

The following treatment was carried out for each of the products tested:Caucasian and Asian volunteers applied a test product once a day, inblind conditions. Clinical and instrumental assessments, by applicationof Sebutape™ patches, were carried out on D0, D14 and D28 and thecontents of these samples of Sebutape™ patches were analysedquantitatively by image analyser (polarimetric imaging).

Determination of the squalene taken in the Sebutape™ patches was carriedout as follows:

The Sebutape™ patches were treated by extraction with 10 ml of ether.The lipid residues were deposited on an HPTLC silica gel nanoplate on analuminium support, one lane of which was reserved for receiving adeposit of 10 μg of squalene standard. The contents of the plates weresubjected to migration in heptane.

The squalene spots were then quantified by densitometry using aninstrument of the ChromatoScan CS-93 (Shimadzu) type. Reading was basedon absorption at 450 nm and the area of the peaks was expressed inarbitrary units in the table of results given below.

Results for pore size: (clinical assessment)

After 28 days of treatment, it was observed that pore size wassignificantly reduced by 30% in the Caucasian volunteers who had appliedthe extract according to Example 1 a) at 2% (p<0.001), a result that ishigher than the 17.5% improvement observed in the zinc gluconate group(p<0.01).

Results for the biosynthesis of squalene: (analysis of the Sebutape™patches)

The results showed that after 28 days of treatment, the content ofsqualene in the sebum had decreased by 13% in the subjects who hadapplied the extract according to Example 1 a) at 2% (p<0.01). Thisimprovement was similar to that obtained with zinc gluconate (−14%,p<0.01) and significantly greater than that obtained with the placebo(p<0.001), for which a slight increase in sebum content was observed(+6%, NS).

Results for the secretion of sebum: (analysis of the Sebutape™ patches)

At 28 days of treatment, the number of active sebaceous glands haddecreased by 7.4% in the subjects who had applied the extract accordingto Example 1 a) at 2% (measurement of the number of spots present on thepatches compared against D0).

Example 4 Evaluation in vivo of the Rebound Effect After Application ofan Orthosiphon stamineus Extract According to the Invention

The experiment was conducted on Caucasian and Asian volunteers accordingto the conditions described in Example 3 for 28 days of treatment (lastapplication on D27 in the evening). Assessments carried out on D30allowed the persistence of the effect of an extract according to theinvention on the production of sebum to be evaluated, two days afterstopping the treatment.

Results for shiny appearance: (clinical assessment)

No rebound effect was observed: two days after stopping the treatment,shiny appearance was significantly reduced by 31% with the extractaccording to Example 1 a) at 2% (p<0.001).

Results for pore size: (clinical assessment)

Two days after stopping the treatment, the decrease in pore size alreadyobserved with the extract according to Example 1 a) at 2% persisted andwas still significant relative to the first day of the study (−16%,p<0.001).

These results demonstrate both the rapidity of action of an extractaccording to the invention and the absence of a rebound effect.

Results for skin texture: (self-evaluation)

Moreover, 2 days after stopping the treatment, 71% of the Asianvolunteers who had applied the extract according to Example 1 a) at 2%declared that there was refinement of their skin grain (p<0.05). Incomparison, only 52% of the volunteers in the group of volunteers whohad applied the positive control (zinc gluconate) noticed an improvementin this parameter.

Results for the secretion of sebum: (analysis of the Sebutape™ patches)

Two days after stopping the treatment, the number of active sebaceousglands had decreased by 14.6% in the subjects who had applied theextract according to Example 1 a) at 2%.

The results are summarized below in Table 2:

TABLE 2 Measurement of the number of spots present on the Sebutape ™patches after 28 days and 2 days after stopping the treatment, comparedagainst D0. Active sebaceous glands, % Dn/D0 D28 2 days after D28 Zincgluconate 1% +8.5% −3.8% Extract according to the invention at 2% −7.4%−14.6%

Example 5 Examples of Preparation of Compositions According to theInvention

Following procedures known by a person skilled in the art, the variousparts A, B, C, D, E, or F were mixed together to prepare a compositionaccording to the present invention. The “products of the invention”represent an Orthosiphon stamineus extract preferably obtained accordingto Example 1 a).

The products of the invention can also be in the form of liposomescontaining 5% of soya lecithin and incorporating a solution ofquaternized soya (600 g final) obtained according to the followingembodiment:

30 g of soya lecithin, 12 g of solution of quaternized soya, and 1.5 gof extract of Orthosiphon stamineus prepared according to Example 1 a)are put in a pill-making machine and diluted in 447 g oflaboratory-grade pure water.

After magnetic stirring for 10 minutes at room temperature, the mixtureis homogenized vigorously for 10 minutes, thus obtaining a liposomalsolution in which the liposomes have an average size which can bebetween 100 and 800 nanometres depending on the precise conditions ofhomogenization.

The suspension is then stirred gently for 1 hour. 90 g of butyleneglycol, 6 g of phenoxyethanol and 6 g of hydroxyethylcellulose (gellingagent) are then added.

Formulation 5a: A Water q.s. 100 Butylene Glycol 2 Glycerol 3 SodiumDihydroxycetyl 2 Phosphate, Isopropyl Hydroxycetyl Ether B GlycolStearate SE 14 Triisononanoin 5 Octyl Cocoate 6 C Butylene Glycol,Methylparaben, 2 Ethylparaben, Propylparaben, pH adjusted to 5.5 DProducts of the invention 0.01-10% Formulation 5b: A Water q.s. 100Butylene Glycol 2 Glycerol 3 Polyacrylamide, Isoparaffin, 2.8 Laureth-7B Butylene Glycol, Methylparaben, 2 Ethylparaben, Propylparaben;Phenoxyethanol, Methylparaben, 2 Propylparaben, Butylparaben,Ethylparaben Butylene Glycol 0.5 D Products of the invention 0.01-10%Formulation 5c: A Carbomer 0.50 Propylene Glycol 3 Glycerol 5 Water q.s.100 B Octyl Cocoate 5 Bisabolol 0.30 Dimethicone 0.30 C Sodium Hydroxide1.60 D Phenoxyethanol, Methylparaben, 0.50 Propylparaben, Butylparaben,Ethylparaben E Perfume 0.30 F Products of the invention 0.01-10%

1. Cosmetic use of an Orthosiphon stamineus extract for preventingand/or reducing and/or delaying the secretion of sebum, in particular ofsqualene.
 2. (canceled)
 3. Cosmetic use according to claim 1 for thecosmetic care and/or treatment of skin described as normal, greasy,having a greasy tendency and/or mixed, and/or of hair described asgreasy, and/or having a greasy tendency.
 4. Use of an Orthosiphonstamineus extract for preparing a pharmaceutical, notably dermatologicalcomposition intended for preventing and/or treating at least onepathology associated with hyperproduction of sebum, notably of squalene.5. Use according to claim 4, in which the pathology is selected from thepathological hyperseborrhoeas, seborrhoeic eczema, and/or hypersecretionin nursing infants, and/or any combination thereof.
 6. Use according toclaim 1 at a concentration between 1.10⁻⁴% and 10% by weight, andadvantageously between 1.10⁻⁴% and 5% by weight of the totalcomposition.
 7. Use according to one of the preceding claims claim 1 ata concentration between 1.10⁻³% and 3% by weight of the totalcomposition.
 8. Use according to one of the preceding claims claim 1, inwhich the Orthosiphon stamineus extract is obtained from leaves.
 9. Useaccording to one of the preceding claims claim 1, in which theOrthosiphon stamineus extract is obtained by hot aqueous extraction,notably by percolation between 30 and 50° C.
 10. Use according to claim1 by application to a surface of the body selected from the skin of theface, including the forehead, the cheeks and/or the chin, of the neck,of the back, of the thorax, of the hands, and/or of the chest. 11.Cosmetic or pharmaceutical, notably dermatological compositioncomprising an Orthosiphon stamineus extract in combination with at leastone agent selected from the seboregulating agents and/or at least oneagent with a complementary property selected from exfoliating agents,keratolytic agents, agents stimulating the synthesis of fibronectin,agents protecting the fibroblast growth factor (FGF2), agentsstimulating the growth of fibroblasts, an antibacterial agent, a sebumabsorber, a comedolytic agent, a local antibiotic, and any mixturethereof.
 12. Composition according to claim 11, in which the Orthosiphonstamineus extract is contained at a concentration between 1.10⁻⁴ and 10%by weight, and advantageously between 1.10⁻⁴ and 5% by weight of thetotal composition.
 13. Composition according to claim 12 at aconcentration between 1.10⁻³ and 3% by weight of the total composition.14. Composition according to claim 11, in which the Orthosiphonstamineus extract is obtained from leaves.
 15. Composition according toclaim 11, in which the Orthosiphon stamineus extract is obtained by hotaqueous extraction, notably by percolation between 30 and 50° C. 16.Composition according to claim 11, in which the seboregulating agent isselected from sarcosine, zinc salicylate, zinc gluconate, azelaic acid,and/or their derivatives and/or any mixture thereof.
 17. Compositionaccording to claim 11, in which the agent with a complementary propertyis selected from AHA, a maize extract, an extract of Hibiscusabelmoschus, a fermented soya extract containing peptides, abiotechnologically modified malt extract, a talc, an absorbent polymer,an extract of Boldo, retinoic acid or a derivative thereof, benzoylperoxide, erythromycin, clindamycin phosphate and any mixture thereof18. Use of a cosmetic composition according to claim 11, for preventingand/or reducing and/or delaying the secretion of sebum, in particular ofsqualene and/or for preventing and/or reducing and/or delaying thedilatation of the pore size of the skin and/or the formation ofblackheads and/or the shiny appearance of the skin and/or of the hairand/or comedogenesis.
 19. Pharmaceutical composition according to claim11 for preventing and/or treating at least one pathology associated withhyperproduction of sebum, notably of squalene, and especiallypathological hyperseborrhoeas, seborrhoeic eczema and/or hypersecretionin nursing infants.
 20. Method of cosmetic care and/or treatmentcomprising the daily topical application of an Orthosiphon stamineusextract for preventing and/or reducing and/or delaying the secretion ofsebum or of a composition according to claim 11 for preventing and/orreducing and/or delaying the secretion of sebum, in particular ofsqualene and/or for preventing and/or reducing the unaesthetic and/orunpleasant and/or uncomfortable manifestations associated with thesecretion of sebum, notably for preventing and/or reducing and/ordelaying the dilatation of the pore size of the skin and/or theformation of blackheads and/or the shiny appearance of the skin and/orof the hair and/or comedogenesis.
 21. Method according to claim 20, inwhich daily topical application is carried out for at least 10 days,preferably for at least 20 days.